%0 Journal Article
%A Aguareles Gorines, José
%A Paraíso Luna, Juan
%A Palomares, Belén
%A Bajo Grañeras, Raquel
%A Navarrete, Carmen
%A Ruiz-Calvo, Andrea
%A García Rincón, Daniel
%A García-Taboada, Elena
%A Guzmán, Manuel
%A Muñoz, Eduardo
%A Galve Roperh, Ismael
%T Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis andprotects against mutant huntingtin-induced neurodegeneration
%D 2019
%@ 2047-9158
%U https://hdl.handle.net/20.500.14352/13611
%X Background: The administration of certain cannabinoids provides neuroprotection in models of neurodegenerativediseases by acting through various cellular and molecular mechanisms. Many cannabinoid actions in the nervoussystem are mediated by CB1 receptors, which can elicit psychotropic effects, but other targets devoid of psychotropicactivity, including CB2 and nuclear PPARγ receptors, can also be the target of specific cannabinoids.Methods: We investigated the pro-neurogenic potential of the synthetic cannabigerol derivative, VCE-003.2, in striatalneurodegeneration by using adeno-associated viral expression of mutant huntingtin in vivo and mouse embryonicstem cell differentiation in vitro.Results: Oral administration of VCE-003.2 protected striatal medium spiny neurons from mutant huntingtin-induceddamage, attenuated neuroinflammation and improved motor performance. VCE-003.2 bioavailability was characterizedand the potential undesired side effects were evaluated by analyzing hepatotoxicity after chronic treatment. VCE-003.2promoted subventricular zone progenitor mobilization, increased doublecortin-positive migrating neuroblasts towardsthe injured area, and enhanced effective neurogenesis. Moreover, we demonstrated the proneurogenic activity ofVCE-003.2 in embryonic stem cells. VCE-003.2 was able to increase neuroblast formation and striatal-like CTIP2-mediated neurogenesis.Conclusions: The cannabigerol derivative VCE-003.2 improves subventricular zone-derived neurogenesis inresponse to mutant huntingtin-induced neurodegeneration, and is neuroprotective by oral administration
%~